1. Field of the Invention
The present invention relates to labeled radiopharmaceuticals.
2. Description of the Related Art
Radiometals (e.g., 64Cu, 89Zr, 68Ga, 86Y and 99mTc) play a pivotal role in nuclear medicine as therapeutic and imaging agents for radiation therapy and labeling of biologically important macromolecules like proteins, peptides and antibodies.
In the recent past, a rapid increase has been noted in both clinical and preclinical studies involving 68Ga-labeled radiopharmaceuticals [Ref. 1-5]. This increase can be attributed to the favorable physical characteristics of 68Ga (Eβmax 1.8 MeV, β+ 89%, T1/2=67.7 minutes) for imaging various rapidly changing processes (proliferation, apoptosis, angiogenesis) and targets (growth hormones, myocardial and pulmonary perfusion, inflammation and infection), and to some extent, to newer, more reliable production and labeling methods [Ref. 1-5]. Gallium-68 labeled somatostatin analogs have already shown their superiority over the existing agent 111In-DTPA-octreotide through enhanced sensitivity, specificity, accuracy and cost effectiveness for the diagnosis of patients with neuroendocrine tumors [Ref. 1, 6-9].
The clinical promise of 68Ga-labeled radiopharmaceuticals clearly warrants growth of the supply of 68Ga to meet the increasing demand in various nuclear medicine facilities. Presently, 68Ga can be produced by two different approaches, (1) solid targetry [Ref. 10,11] and (2) the 68Ge/68Ga generator [Ref. 12]. The former requires high capital cost and expertise and specialized cyclotron facilities that accommodate solid targets, whereas, the latter is more broadly accessible in nuclear medicine facilities not equipped with an on-site cyclotron. The simplicity and lower capital cost of the 68Ge/68Ga generator have made it more popular among the nuclear medicine facilities with relatively lower number of requirements for 68Ga labeled doses [Ref. 1, 12]. However, the breakthrough of trace quantities of the long-lived 68Ge parent isotope (t1/2=271 days) into the eluted 68Ga remains a concern [Ref. 13]. Furthermore, with increasing applicability of 68Ga-labeled radiopharmaceuticals, one can foresee a need for alternative production methods to meet the increasing demand especially for the relatively busy nuclear medicine centers having an on-site cyclotron. There have been previous attempts to produce 68Ga using a cyclotron, initially employing a solid target method using 68Zn electrodeposition on a copper substrate [Ref. 10, 14] and more recently using a solution target containing an enriched 68ZnCl2 solution [Ref. 15]. The solid target methods require a lengthy separation step, which is not optimal for short-lived isotopes like 68Ga, as well as expensive solid target infrastructure.
Thus, needed in the art are methods and systems to extend the applicability of the solution target approach to the production of 68Ga and other radiometals using a low energy cyclotron.